This project is concerned with an ultrastructural analysis of severed axons and regenerating axon sprouts in the mammalian spinal cord and optic nerve. The investigation originally sought to determine whether a cell mediated immune response to brain antigens blocked regeneration at the site of the lesion. Experimental manipulation of the immune response by the use of drugs and injections of brain antigens have so far failed to alter either the initial regenerative response or the subsequent involution of axon sprouts. Current studies thus provide little support for the concept of an immune impediment to axon regeneration, but they have revealed new aspects of retrograde axon degeneration, indicating glial cells in the mammalian brain and spinal cord constitute an intrinsic-impediment to continued growth of axons. Preliminary results from experiments in which dorsal roots in the cat were crushed and allowed to regenerate support this view. Axon sprouts grow well in peripheral nerve portions of the root, but fail to penetrate central nervous tissue of the spinal cord. If experiments in progress confirm that glial cells in the CNS are incapable either of promoting the growth of axon sprouts or sustaining portions of the central axon devoid of collaterals, it would appear that prospects for achieving functional regeneration through conventional experimental approaches are remote.